Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae)

Abstract

Background Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC.ResultsResults indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 μg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 μg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 μg/mL for (1), 34.15 μg/mL for (2) and 45.66 μg/mL for (3), compared to galantamine (IC50 of 8.22 μg/mL) used as positive control.ConclusionThe limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Chemical constituents from the fruits of Citrus unshiu and their inhibitory effects on acetylcholinesterase

“…There have been widespread efforts to identify new AChE inhibitors from natural sources, but only limited work has focused on limonoids. Recently, three limonoids isolated from Trichilia welwitschii were reported to show weak to moderate inhibitory effects on AChE activity [14,29]. Our present findings suggest for the first time that another limonoid, methyl nomilinate (1), is a potential AChE activity inhibitor.…”

“…Compound 1 is a highly oxygenated limonoid compound with a prototypical structure consisting of four six-membered rings and a furan ring. This type of limonoid compound is abundant in citrus fruit and other plants from the families Rutaceae and Meliaceae [14]. Limonoids have been reported to exhibit diverse bioactivity including insecticidal, antibacterial, antifungal, antiviral and anticancer effects [28].…”

“…In addition, we discovered a new flavonoid glycoside, limocitrunshin, together with other flavonoids, and evaluated their inhibitory effects on renal cell damage and nitric oxide (NO) production [7]. NO is an important pro-inflammatory mediator that can accelerate the appearance of some neurodegenerative disorders such as AD [14]. Thus, the fruit of C. unshiu containing compounds with NO inhibitory properties may be a promising candidate for providing therapeutic agents for AD.…”

Nimbolide Inhibits Nuclear Factor-КB Pathway in Intestinal Epithelial Cells and Macrophages and Alleviates Experimental Colitis in Mice

“…It is usually found in plant families of Meliaceae and Rutaceae (Roy and Saraf, 2006;Tundis et al, 2014). Limonoid compounds have been shown to have various medical effects such as antiviral, antibacterial, antifungal, antimalarial, antiinflammatory, and anticancer (Chen et al, 2015;Dzoyem et al, 2015;Koul et al, 2004;Miller et al, 2004;Nakagawa et al, 2001).…”

Nitric Oxide Inhibitory and Cytotoxic Activities of Spice Essential Oils

“…However, the overproduction of NO can lead to cytotoxicity and chronic inflammation (Dzoyem et al, 2015). The unnecessary NO and inflammatory mediators are produced by continuously activated macrophages in chronic inflammatory processes.…”